We could get one or two films more out of the original cast, and perhaps a third that's a crossover with Fantastic Four.

By that point, it will probably be time for a total reboot.

And by that time, Marvel/Disney may be more involved. I don't know how long Singer and Vaughn will stay involved before being pulled away by other projects. It's worth noting that Marvel are slowly getting back many of the other rights - Ghost Rider has now gone back to them from Sony as well as Fox's Daredevil. In the next decade there might at least be more Marvel/Fox crossovers.

Who knows how long Hugh, Halle etc will stay involved. They're getting Arnie back into the Conan role so it's possible for veteran actors to stay with (or return to) a franchise.